Authors: Luo, Linlin et al.
Anesthesiology, August 28, 2025. DOI: 10.1097/ALN.0000000000005735
This study investigated whether a shared neural mechanism underlies two hallmark effects of general anesthesia—unconsciousness and respiratory depression. The research focused on the parafacial zone (PZ), a GABAergic region of the brainstem known to promote sleep and modulate breathing, to determine its role in mediating sevoflurane-induced effects on arousal and respiration.
Using chemogenetic and optogenetic techniques in 95 adult male mice, investigators selectively activated or inhibited PZ GABAergic neurons while monitoring anesthetic sensitivity, electroencephalographic activity, and respiratory parameters. Activation of these neurons markedly increased anesthetic potency, reducing the concentration of sevoflurane required for loss of righting reflex (0.735% vs. 1.601%) and shifting the anesthetic dose-response curve leftward. Mice with PZ activation entered anesthesia faster and took longer to recover, exhibiting increased EEG delta power consistent with a deeper anesthetic state.
At the same time, respiratory rate declined dramatically (from 471 to 183 breaths per minute), demonstrating strong suppression of respiratory drive. Brief optogenetic stimulation of PZ GABAergic neurons during anesthesia enhanced cortical burst suppression and further slowed respiration, indicating that the same neural population modulates both anesthetic depth and breathing. Inhibition of these neurons produced the opposite effect, reducing anesthetic potency. Additionally, activating PZ GABAergic neurons in awake mice induced a drowsy, analgesic state accompanied by respiratory slowing, even without complete loss of consciousness.
These findings identify the PZ GABAergic network as a central hub that links anesthetic-induced unconsciousness with respiratory depression, suggesting that anesthetic agents exploit existing sleep–respiration regulatory circuits.
What You Should Know:
The parafacial zone serves as a shared control center for both consciousness and respiration during anesthesia. Activation of its GABAergic neurons deepens anesthesia while suppressing breathing, offering new insight into the neural basis of anesthetic-induced respiratory depression and potential targets for safer anesthetic management.
Thank you to Anesthesiology for publishing this groundbreaking work revealing a common neural substrate for loss of consciousness and respiratory suppression under anesthesia.